LY 117018 is a nonsteroidal compound which has been shown to antagonize more effectively than tamoxifen the effects of estradiol in rats and mice. We have further defined the properties of this compound on cell growth and progesterone receptor (PR) induction and have compared inhibitory effects to relative binding affinity in a human breast cancer cell line. In MCF-7 cells, LY 117018 [(6-hydroxy-2-(p-hydroxyphenyl)benzo[b]thien-3-yl-p-(2-pyrrolidinyl)ethoxy phenyl ketone] is devoid of estrogenic effects, has a greater affinity for the estrogen receptor (ER) than tamoxifen at 4 C, and is 100-1000 times more potent than tamoxifen at inhibiting cell growth. While tamoxifen has been reported to induce PR, a purported estrogen effect, the LY 117018 compound failed to induce PR using a broad range of concentrations. The direct antagonistic effect of LY 117018 was demonstrated by the use of varying concentrations of LY 117018 and estradiol concomitantly. We conclude that LY 117018 is a very effective antiestrogen devoid of any stimulatory effects among these parameters tested.
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